APPLICANT'S ABSTRACT: This application seeks five years of renewed funding for a research program aimed at understanding the etiology of alcoholism from a developmental behavioral genetic perspective. We hypothesize that an inherited liability to alcoholism can be expressed early in adolescence as: 1) personality deviations, 2) increased rate of behavioral disorder, and 3) differences in psychophysiological markers. We hypothesize further that these phenotypic markers of liability influence alcoholism risk in part by increasing the likelihood that an individual is both exposed to and affected by experimental risk factors during adolescence. During the first four years of funding, 675 twin-families consisting of a pair of adolescent female twins, their mothers and their fathers will have completed a day-long intake assessment that includes extensive assessment of: 1) psychiatric status and substance-abuse history, 2) personality/temperament organized around three broad dimensions of personality (Positive Emotionality, Negative Emotionality, and Behavioral Constraint), 3) psychophysiology markers (including brain event-related potentials [P3], resting EEG, autonomic arousal and emotional modulation, and eye-tracking dysfunction), and 4) environmental factors (including family climate, peer group, and cognitive risk factors). At intake, the Twins are either age 11 (i.e., an age prior to initial experimentation with alcohol) or 17 (i.e., an age prior to the attainment of adulthood and the initial establishment of adult patterns of g). Approximately 40% of the twins are expected to be at high-risk for developing alcoholism or a related disorder by virtue of having a biological parent who is alcoholic. During the next five years we propose to: 1) complete in-person follow-up assessments at three year intervals following the intake assessment, and 2) complete analysis of the intake as well as initiate analysis of the first follow-up data. The in-person follow-up assessments will closely parallel the intake assessments and allow us to determine who among the younger cohort initiated early and heavy alcohol use, and who among the older cohort went on to develop alcohol dependence in adulthood. The focus of the proposed data analysis include: 1) a precise determination of the offspring correlates of parental alcoholism and whether those offspring correlates are moderated by gender and parental alcoholism severity, 2) completion of univariate biometrics analysis of the twin data to determine the extent to which risk factor variance is associated with genetic, shared environmental and non-shared environmental factors, 3) completion of multivariate biometrics analysis of the twin data aimed at identifying the factors that might underlie the heritability and environmentality of key outcome measures, and 4) application of genotype-environment interaction models.